甲状腺激素β受体

甲状腺激素β受体（TR-β，或THR-β）也称为核受体亚家族1，A 组，成员2（NR1A2），是一种核受体蛋白，在人类中由THR-β基因编码。^[6][7]

THRB
已知的結構 PDB 直系同源搜索: PDBe RCSB PDBID列表 1BSX、​1N46、​1NAX、​1NQ0、​1NQ1、​1NQ2、​1NUO、​1Q4X、​1R6G、​1XZX、​1Y0X、​2J4A、​2NLL、​2PIN、​3D57、​3GWS、​3IMY、​3JZC、​4ZO1
識別號
别名	THRB；, C-ERBA-2, C-ERBA-BETA, ERBA2, GRTH, NR1A2, PRTH, THR1, THRB1, THRB2, thyroid hormone receptor beta, TRbeta
外部ID	OMIM：190160 MGI：98743 HomoloGene：36025 GeneCards：THRB
為以下藥物的標靶
DL-3,3',5'-triiodothyronine、​tiratricol、​三碘甲腺原氨酸、​左旋甲狀腺素鈉^[1]
基因位置（人类） 染色体 3號染色體^[2] 基因座 3p24.2 起始 24,117,153 bp^[2] 终止 24,495,756 bp^[2]
基因位置（小鼠） 染色体 小鼠14号染色体^[3] 基因座 14|14 A1 起始 4,431,611 bp^[3] 终止 4,809,435 bp^[3]
RNA表达模式
查阅更多表达数据
基因本體 分子功能 • sequence-specific DNA binding • transcription corepressor activity • 鋅離子結合 • 金屬離子結合 • steroid hormone receptor activity • 血浆蛋白结合 • 酶结合 • chromatin DNA binding • thyroid hormone binding • DNA结合转录因子活性 • DNA结合 • DNA-binding transcription factor activity, RNA polymerase II-specific • transcription cis-regulatory region binding • RNA polymerase II transcription regulatory region sequence-specific DNA binding • 转录因子结合 • nuclear receptor coactivator activity • signaling receptor activity • nuclear receptor activity 細胞組分 • 核质 • 细胞核 • nuclear body • RNA polymerase II transcription regulator complex 生物學過程 • regulation of transcription, DNA-templated • regulation of heart contraction • female courtship behavior • regulation of transcription by RNA polymerase II • negative regulation of transcription by RNA polymerase II • sensory perception of sound • type I pneumocyte differentiation • negative regulation of female receptivity • animal organ morphogenesis • transcription initiation from RNA polymerase II promoter • negative regulation of transcription, DNA-templated • positive regulation of transcription by RNA polymerase II • steroid hormone mediated signaling pathway • intracellular receptor signaling pathway • transcription, DNA-templated • negative regulation of eye photoreceptor cell development • retinal cone cell development • retinal cone cell apoptotic process • multicellular organism development • hormone-mediated signaling pathway • 细胞分化 • thyroid gland development • response to lipid • thyroid hormone mediated signaling pathway Sources:Amigo / QuickGO
直系同源
物種	人類	小鼠
Entrez	7068	21834
Ensembl	ENSG00000151090	ENSMUSG00000021779
UniProt	P10828	P37242
mRNA​序列	​NM_000461 ​NM_001128176 ​NM_001128177 ​NM_001252634 ​NM_001354708 ​NM_001354709 ​NM_001354710 ​NM_001354711 ​NM_001354712 ​NM_001354713 ​NM_001354714 ​NM_001354715 ​NM_001374822 ​NM_001374823 ​NM_001374824 ​NM_001374825 ​NM_001374826 ​NM_001374827	NM_001113417 ​NM_009380
蛋白序列	NP_000452 ​NP_001121648 ​NP_001121649 ​NP_001239563 ​NP_001341637 ​NP_001341638 ​NP_001341639 ​NP_001341640 ​NP_001341641 ​NP_001341642 ​NP_001341643 ​NP_001341644 ​NP_001361751 ​NP_001361752 ​NP_001361753 ​NP_001361754 ​NP_001361755 ​NP_001361756	NP_001106888 ​NP_033406
基因位置​（UCSC）	Chr 3: 24.12 – 24.5 Mb	Chr 14: 4.43 – 4.81 Mb
PubMed​查找	^[4]	^[5]
維基數據
檢視/編輯人類 檢視/編輯小鼠

功能

该基因编码的蛋白质为三碘甲腺原氨酸的核激素受体。它是甲状腺激素的多种受体之一，已被证明可以调节甲状腺激素的生物活性。小鼠基因敲除研究表明，不同的受体虽然具有一定程度的冗余，但可能介导甲状腺激素的不同功能。已知该基因的缺陷是导致：广泛性 甲状腺激素抵抗（GTHR）的成因。该综合征疾病的特征为：甲状腺肿大；循环甲状腺激素（T₃-T₄）水平增加；同时促甲状腺激素（TSH）正常或略微升高。现已发现到该基因的几种转录变体，但迄今为止只观察到一种的全长天然基因。^[8]

基因互作

甲状腺激素β受体已被证明与以下存在基因相互作用：

• BRD8,^[9]
• CCND1,^[10]
• NCOA1,^[11][12]
• NCOA6,^{[13][14][15][16]}
• NCOR2,^[11][17][18]
• NR2F6,^[19]
• PPARGC1A,^[20] and
• RXRA.^[9][12]

参考文献

1. 對Thyroid hormone receptor beta起作用的藥物；在維基數據上查看/編輯參考. 
2. GRCh38: Ensembl release 89: ENSG00000151090 - Ensembl, May 2017
3. GRCm38: Ensembl release 89: ENSMUSG00000021779 - Ensembl, May 2017
4. Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
5. Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
6. Entrez Gene: THRA thyroid hormone receptor, alpha (erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian). 
7. Sakurai A, Nakai A, DeGroot LJ. Structural analysis of human thyroid hormone receptor beta gene. Mol. Cell. Endocrinol. June 1990, 71 (2): 83–91. PMID 1973914. S2CID 54389426. doi:10.1016/0303-7207(90)90245-4. 
8. Entrez Gene: THRB thyroid hormone receptor, beta (erythroblastic leukemia viral (v-erb-a) oncogene homolog 2, avian). 
9. Monden T, Wondisford FE, Hollenberg AN. Isolation and characterization of a novel ligand-dependent thyroid hormone receptor-coactivating protein. J. Biol. Chem. November 1997, 272 (47): 29834–41. PMID 9368056. doi:10.1074/jbc.272.47.29834  . 
10. Lin HM, Zhao L, Cheng SY. Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors. J. Biol. Chem. August 2002, 277 (32): 28733–41. PMID 12048199. doi:10.1074/jbc.M203380200  . 
11. Liu Y, Takeshita A, Misiti S, Chin WW, Yen PM. Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors. Endocrinology. October 1998, 139 (10): 4197–204. PMID 9751500. doi:10.1210/endo.139.10.6218  . 
12. Jeyakumar M, Tanen MR, Bagchi MK. Analysis of the functional role of steroid receptor coactivator-1 in ligand-induced transactivation by thyroid hormone receptor. Mol. Endocrinol. June 1997, 11 (6): 755–67. PMID 9171239. doi:10.1210/mend.11.6.0003  . 
13. Lee SK, Jung SY, Kim YS, Na SY, Lee YC, Lee JW. Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2. Mol. Endocrinol. February 2001, 15 (2): 241–54. PMID 11158331. doi:10.1210/mend.15.2.0595  . 
14. Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, Jung YK, Kallioniemi OP, Kononen J, Trent JM, Azorsa D, Jhun BH, Cheong JH, Lee YC, Meltzer PS, Lee JW. A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. J. Biol. Chem. November 1999, 274 (48): 34283–93. PMID 10567404. doi:10.1074/jbc.274.48.34283  . 
15. Ko L, Cardona GR, Chin WW. Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator. Proc. Natl. Acad. Sci. U.S.A. May 2000, 97 (11): 6212–7. Bibcode:2000PNAS...97.6212K. PMC 18584  . PMID 10823961. doi:10.1073/pnas.97.11.6212  . 
16. Ko L, Cardona GR, Iwasaki T, Bramlett KS, Burris TP, Chin WW. Ser-884 adjacent to the LXXLL motif of coactivator TRBP defines selectivity for ERs and TRs. Mol. Endocrinol. January 2002, 16 (1): 128–40. PMID 11773444. doi:10.1210/mend.16.1.0755  . 
17. Tagami T, Lutz WH, Kumar R, Jameson JL. The interaction of the vitamin D receptor with nuclear receptor corepressors and coactivators. Biochem. Biophys. Res. Commun. December 1998, 253 (2): 358–63. PMID 9878542. doi:10.1006/bbrc.1998.9799. 
18. Ando S, Sarlis NJ, Krishnan J, Feng X, Refetoff S, Zhang MQ, Oldfield EH, Yen PM. Aberrant alternative splicing of thyroid hormone receptor in a TSH-secreting pituitary tumor is a mechanism for hormone resistance. Mol. Endocrinol. September 2001, 15 (9): 1529–38. PMID 11518802. doi:10.1210/mend.15.9.0687  . 
19. Zhu XG, Park KS, Kaneshige M, Bhat MK, Zhu Q, Mariash CN, McPhie P, Cheng SY. The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid hormone nuclear receptor function. Mol. Cell. Biol. April 2000, 20 (7): 2604–18. PMC 85476  . PMID 10713182. doi:10.1128/MCB.20.7.2604-2618.2000. 
20. Wu Y, Delerive P, Chin WW, Burris TP. Requirement of helix 1 and the AF-2 domain of the thyroid hormone receptor for coactivation by PGC-1. J. Biol. Chem. March 2002, 277 (11): 8898–905. PMID 11751919. doi:10.1074/jbc.M110761200  . 

扩展阅读

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• González-Sancho JM, García V, Bonilla F, Muñoz A. Thyroid hormone receptors/THR genes in human cancer. Cancer Lett. 2003, 192 (2): 121–32. PMID 12668276. doi:10.1016/S0304-3835(02)00614-6. 
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